Effects of dissolved oxygen tension and agitation rate on the production of heat-shock protein glycoprotein 96 by MethA tumor cell suspension culture in stirred-tank bioreactors.
Heat-shock protein glycoprotein (gp96) serves as a natural adjuvant for chaperoning antigenic peptide into the immune surveillance pathway. In our laboratory, MethA tumor cell suspension culture process has been recently developed for gp96 production in spinner flask. In this work, effects of dissolved oxygen tension (DOT) and agitation rate on this process were studied in stirred-tank bioreactor. The optimal conditions for gp96 production were different with those for MethA tumor cell growth. MethA tumor cell growth pattern was not much changed by various levels of DOT and agitation rate, while gp96 biosynthesis was more sensitive to DOT and agitation rate. Compared with 50% of DOT, the production and specific productivity of gp96 was increased by 27 and 66% at 10% of DOT, respectively. Compared with the agitation rate of 100 rpm, the production and volumetric productivity of gp96 was increased by 48 and 144% at the agitation rate of 200 rpm, respectively. Low DOT (i.e., 10% of air saturation) and high agitation rate (i.e., 200 rpm) were identified to be favorable for gp96 biosynthesis. The results of this work might be useful to scale-up the bioprocess into the pilot scale.
Tang
Ya-Jie
YJ
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. yajietang@hotmail.com
Li
Hong-Mei
HM
Hamel
Jean-François P
JF
D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D001698:Biomedical Engineering; D019149:Bioreactors; D002452:Cell Count; D045744:Cell Line, Tumor; D002470:Cell Survival; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D010100:Oxygen; D012513:Sarcoma, Experimental / Q000378:metabolism / Q000473:pathology
D000951:Antigens, Neoplasm; C052646:sarcoma glycoprotein gp96 rejection antigens; D005973:Glutamine; D005947:Glucose; D010100:Oxygen